Steviol is the colonic metabolite of the natural sweetener steviol glycosides. It does not diffuse to the blood and the half maximal inhibitory concentration of steviol is longer compared with that of current chemotherapy agents, including 5-fluorouracil and doxorubicin. The present study demonstrated that steviol inhibits the proliferation of the human osteosarcoma U2OS cell line in a dose- and time-dependent manner, and that the inhibition rate is comparative with that of doxorubicin and 5-fluorouracil. The mechanism of this anticancer activity is also investigated. The results indicated that steviol inhibits U2OS cells through inducing G1 phase cell cycle arrest, downregulating the ability of colony formation via a mitochondrial apoptotic pathway, which was indicated by an increase of the Bax/Bcl-2 ratio and activation of cyclin-dependent kinase inhibitor 1, tumor protein 53 and cyclin-dependent kinase; whereas a Survivin and Caspase 3-independent mechanism was involved. Considering that steviol appears minimally in the plasma during metabolism, and possesses a median lethal dose of 100-fold greater compared with that of 5-fluorouracil, it may become a potential chemotherapy agent.
Acute respiratory distress syndrome (ARDS) is a common lung disorder that involves severe inflammatory damage in the pulmonary barrier, but the underlying mechanisms remain elusive. Here, we demonstrated that pulmonary macrophages originating from ARDS patients and mice caused by bacteria were characterized by increased expression of ferroportin (FPN). Specifically deleting FPN in myeloid cells conferred significant resistance to bacterial infection with improved survival by decreasing extracellular bacterial growth and preserving pulmonary barrier integrity in mice. Mechanistically, macrophage FPN deficiency not only limited the availability of iron to bacteria, but also promoted tissue restoration via growth factor amphiregulin, which is regulated by cellular iron-activated Yes-associated protein signaling. Furthermore, pharmacological treatment with C-Hep, the self-assembled N-terminally cholesterylated minihepcidin that functions in the degradation of macrophage FPN, protected against bacteria-induced lung injury. Therefore, therapeutic strategies targeting the hepcidin-FPN axis in macrophages may be promising for the clinical treatment of acute lung injury.
Purpose: Test the content determination of total saponins in different parts of the plant Paris Polyphylla Var. Chinensis. Method: Take dioscin as reference substance and adopts ultraviolet spectrophotometry on the place of 310.5 nm to test the content determination of total saponins on different parts of the plant Paris Polyphylla Var. Chinensis. Results: the linearity of dioscin in the scope of 0.128mg~0.768mg is good, and the regression equation is A=3.1775C+0.2668(r=0.9994); the test results of average recovery shows that the average recovery ratio is 101.13%, and RSD is 2.31%(n=6). Conclusion: there are larger differences in the content determination of total saponins on different parts of the plant Paris Polyphylla Var. Chinensis; among them, the content in the rhizome of Paris Polyphylla Var. Chinensis is the highest 2.021%, the secondary high content is in the root 0.263%, while dioscin is not detected in the terrestrial stem and leaves.
Sepsis is a leading cause of death in critical illness, and its pathophysiology varies depending on preexisting medical conditions. Here we identified nonalcoholic fatty liver disease (NAFLD) as an independent risk factor for sepsis in a large clinical cohort and showed a link between mortality in NAFLD-associated sepsis and hepatic mitochondrial and energetic metabolism dysfunction. Using in vivo and in vitro models of liver lipid overload, we discovered a metabolic coordination between hepatocyte mitochondria and liver macrophages that express triggering receptor expressed on myeloid cells-2 (TREM2). Trem2-deficient macrophages released exosomes that impaired hepatocytic mitochondrial structure and energy supply because of their high content of miR-106b-5p, which blocks Mitofusin 2 (Mfn2). In a mouse model of NAFLD-associated sepsis, TREM2 deficiency accelerated the initial progression of NAFLD and subsequent susceptibility to sepsis. Conversely, overexpression of TREM2 in liver macrophages improved hepatic energy supply and sepsis outcome. This study demonstrates that NAFLD is a risk factor for sepsis, providing a basis for precision treatment, and identifies hepatocyte-macrophage metabolic coordination and TREM2 as potential targets for future clinical trials.
Abstract In mammals, maternal-to-zygotic transition (MZT), or oocyte-to-embryo transition, begins with oocyte meiotic resumption due to the sequential translational activation and destabilization of dormant maternal transcripts stored in the ooplasm. It then continues with the elimination of maternal transcripts during oocyte maturation and fertilization and ends with the full transcriptional activation of the zygotic genome during embryonic development. A hallmark of MZT in mammals is its reliance on translation and the utilization of stored RNAs and proteins, rather than de novo transcription of genes, to sustain meiotic maturation and early development. Impaired maternal mRNA clearance at the onset of MZT prevents zygotic genome activation and causes early arrest of developing embryos. In this review, we discuss recent advances in our knowledge of the mechanisms whereby mRNA translation and degradation are controlled by cytoplasmic polyadenylation and deadenylation which set up the competence of maturing oocyte to accomplish MZT. The emphasis of this review is on the mouse as a model organism for mammals and BTG4 as a licensing factor of MZT under the translational control of the MAPK cascade.
Journal Article Expression of Iμ-Cγ hybrid germline transcripts subsequent to immunoglobulin heavy chain class switching Get access Suzanne C. Li, Suzanne C. Li 1Departments of Pediatrics630 West 168th Street, New York, NY 10032, USA Correspondence to S C. Li Search for other works by this author on: Oxford Academic PubMed Google Scholar Paul B. Rothman, Paul B. Rothman 2Departments of Microbiology and Medicine630 West 168th Street, New York, NY 10032, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Jue Zhang, Jue Zhang 4The Howard Hughes Medical Institute, The Children's Hospital and The Department of Genetics and Center for Blood Research, Harvard Medical SchoolBoston, MA 02115, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Christina Chan, Christina Chan 3Departments of Biochemistry630 West 168th Street, New York, NY 10032, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar David Hirsh, David Hirsh 3Departments of Biochemistry630 West 168th Street, New York, NY 10032, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Frederick W. Alt Frederick W. Alt 4The Howard Hughes Medical Institute, The Children's Hospital and The Department of Genetics and Center for Blood Research, Harvard Medical SchoolBoston, MA 02115, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar International Immunology, Volume 6, Issue 4, April 1994, Pages 491–497, https://doi.org/10.1093/intimm/6.4.491 Published: 01 April 1994 Article history Received: 14 September 1993 Accepted: 05 November 1993 Published: 01 April 1994
The paper reviewed meanings, examples, evolution and genetic traits of plant tolerance against insect pests and its potential mechanisms, as well as abiotic and biotic factors affecting expression of plant tolerance. Potential mechanisms of tolerance including photosynthetic activity, reallocation of available assimilates, change in inner hormone, compensatory growth and activation of dormant meristems, utilization of stored reserves, and changes in plant phenology and plant architecture after the damage. It has been found that there is no direct relationship between photosynthetic activity change of plants after insect pest damage and its tolerance: for some plants the photosynthetic activity is increased, some unaffected, or even reduced. After damage, assimilates of tolerant plants are utilized to the greatest extent, dormant meristems is activated and overcompensation is induced. Insect damage induces a significantly increased supply of leaf cytokinins or root-derived cytokinins in damage place of tolerant plants. Less change in plant phenology may be one of the more widespread mechanisms of tolerance. Plant size, leaf morphology, root-shoot rations, stem number and so on are related to its tolerance. Main factors affecting tolerance expression are temperature, global CO (2) levels, soil nutrient available levels, agrochemicals, plant ages, distribution type and feeding strategies of insects, plant mutualisms, pollinators, endophytic fungi, mycorrhizal fungi and facilitating plants. Under different temperatures the same plants may have different tolerance to the same pest species. The main cause is that change of temperature results in allocation and reallocation of available assimilates and effects of spiracle closing on gas exchange and photosynthetic ability. Plants grown in high CO (2) concentration has stronger tolerance. Soil nutrient level has stronger effects on plant tolerance expression than temperature. High concentration of phosphorus and potassium increases tolerance level. The distribution type of insects within a field can affect plant compensation for damage, and feeding pattern of insects, pollinator movement, infection of endophytic fungi and mycorrhizal fungi can also influence plant tolerance. The importance and application prospects of plant tolerance in integrated pest management were also discussed.
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